ClinVar Miner

Submissions for variant NM_153704.6(TMEM67):c.88C>T (p.Leu30Phe)

gnomAD frequency: 0.00001  dbSNP: rs1376394849
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001947810 SCV002197338 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2022-06-01 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 30 of the TMEM67 protein (p.Leu30Phe). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with TMEM67-related conditions. ClinVar contains an entry for this variant (Variation ID: 1416073). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TMEM67 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV002281199 SCV002569423 uncertain significance not provided 2022-03-01 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV002491887 SCV002780783 uncertain significance COACH syndrome 1; Joubert syndrome 6; Meckel syndrome, type 3; RHYNS syndrome; Bardet-Biedl syndrome 14; Nephronophthisis 11 2021-12-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV002557716 SCV003717357 uncertain significance Inborn genetic diseases 2022-06-27 criteria provided, single submitter clinical testing The c.88C>T (p.L30F) alteration is located in exon 1 (coding exon 1) of the TMEM67 gene. This alteration results from a C to T substitution at nucleotide position 88, causing the leucine (L) at amino acid position 30 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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